Disturbance of cerebellar synaptic maturation in mutant mice lacking BSRPs, a novel brain-specific receptor-like protein family

Disturbance of cerebellar synaptic maturation in mutant mice lacking BSRPs, a novel brain-specific receptor-like protein family
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DOI:
10.1016/j.febslet.2006.06.043
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发表时间:
2006-07-24
期刊:
影响因子:
3.5
通讯作者:
Takeshima, Hiroshi
Takeshima, Hiroshi
中科院分区:
生物学3区
文献类型:
--
作者:
Miyazaki, Taisuke;Hashimoto, Kouichi;Takeshima, Hiroshi

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通过DNA克隆,我们在哺乳动物基因组中鉴定了BSRP(脑特异性受体样蛋白)家族的三个成员。BSRPs主要表达于神经元的索马体和树突,并定位于内质网。BSRPs的表达水平似乎在出生后小脑成熟过程中波动很大。缺乏BSRP成员的三重基因敲除小鼠表现出运动不协调,浦肯野细胞(PC)经常受到突变小脑中具有不同神经元起源的多个攀爬纤维的支配。此外,蛋白激酶C α(PKC α)的磷酸化水平显着下调的突变小脑。由于小脑的成熟和可塑性需要代谢型谷氨酸受体信号传导和由此产生的PKC激活,BSRPs可能参与支持PC中PKC激活的ER功能。(c)2006年欧洲生物化学学会联合会。Elsevier B.V.出版,保留所有权利。
By DNA cloning, we have identified the BSRP (brain-specific receptor-like proteins) family of three members in mammalian genomes. BSRPs were predominantly expressed in the soma and dendrites of neurons and localized in the endoplasmic reticulum (ER). Expression levels of BSRPs seemed to fluctuate greatly during postnatal cerebellar maturation. Triple-knockout mice lacking BSRP members exhibited motor discoordination, and Purkinje cells (PCs) were often innervated by multiple climbing fibers with different neuronal origins in the mutant cerebellum. Moreover, the phosphorylation levels of protein kinase C alpha (PKC alpha) were significantly downregulated in the mutant cerebellum. Because cerebellar maturation and plasticity require metabotropic glutamate receptor signaling and resulting PKC activation, BSRPs are likely involved in ER functions supporting PKCa activation in PCs. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.